Ion analysis devices such as mass spectrometers and the like are utilized to perform component analyses on a biological sample such as blood, urine and the like. In a typical example, a biological sample is analyzed through pretreatment process, separation process using LC (Liquid Chromatograph), and mass spectrometry process in this order. In the pretreatment process, deproteinization of the biological sample, concentration of an analyte and the like are performed. In the separation process using LC, an analyte is separated from other substances by use of a difference in interaction with column. In LC, water and/or an organic solvent such as methanol and/or the like are used, and solvent composition is chosen to be suitable for separation of an analyte. According to the conditions of solvent composition, the rate of solvent flow, a column type, a column temperature and/or the like, an analyte passes through LC within a unique retention time, which is then introduced into the mass spectrometer. In the mass spectrometry process, an analyte is ionized under atmospheric pressures, and analyte ions are introduced into a vacuum, and then are separated and detected according to the mass-to-charge ratio m/z. The analytes are classified based on the measured retention time and the mass-to-charge ratio m/z, and the analytes are quantitated based on measured signal strength.
For ionization techniques used for a liquid sample using an ion source of an ion analysis device, a technique of using an atomizer to atomize and spray liquid is used. In Electrospray ionization (ESI), a liquid sample is passed through a small tube and high voltage is applied to an outlet of the small tube. The liquid sample is electrically charged at the high voltage, so that the liquid sample at the outlet of the small tube is atomized in a mist form due to electric repulsion to produce charged droplets. In ESI, a nebulizer gas and a heated gas flow coaxially with the liquid sample. The nebulizer gas allows the liquid sample to be stably sprayed. The solvent in the sprayed charged droplets is volatilized, so that the analyte in the droplets is ionized. The heated gas accelerates vaporization of the solvent. The vaporization efficiency depends on the solvent composition and the flow rate of the liquid sample. Therefore, under the condition that water makes up a high percentage in the composition or the condition that the flow rate is high, the vaporization efficiency is decreased and thus the ionic strength is reduced as compared with the amount of charged droplets. The vaporization efficiency of the solvent is also decreased by a matrix-derived component of the sample such as blood, urine or the like and thus the ionic strength is reduced. In the case of low vaporization efficiency and a large amount of charged droplets, the vaporization can be accelerated by increasing the temperature and/or the flow rate of the heated gas. On the other hand, excessive heating brings the liquid sample to a boil, causing an unstable ionic strength. Because of this, there is a need to select heated-gas conditions appropriate for the solvent composition and the flow rate.
In addition to ESI, the ionization techniques employed include APCI (Atmospheric Pressure Chemical Ionization, APPI (Atmospheric Pressure Photoionization), and the like. In APCI, after a liquid sample is atomized with a nebulizer gas and the solvent is volatilized with a heated gas, the sample is ionized with a corona discharge. In APPI, a liquid sample is atomized, which is then irradiated with light to be ionized. Similarly to ESI, there is a need in APCI and APPI for selection of heated-gas conditions appropriate for the solvent composition and the flow rate. APCI and APPI, however, differ from ESI in that high voltage is not applied at a small-tube's outlet. Because of this, in APCI and APPI, the droplets are electrically neutral.
Patent Literature 1 describes an ion guide having an outlet for ions and an outlet for airflow. In the ion guide, an ion transport mechanism transports ions from an ion source under atmospheric pressures to a mass spectrometer under a high vacuum, and the ion transport mechanism is used to transport ions by an electric field under pressure ranging from several tens to several thousands of Pa. The ions produced by the ion source pass, together with ambient gas, through a vacuum chamber entrance to enter the ion guide because of a pressure difference between the ion source and the ion guide. The airflow containing the ions is adiabatically expanded to be accelerated to hypersonic speeds, and travels in straight line within the ion guide. In Patent Literature 1, two ion guides with different central axes are connected. Low-mass ions are guided by an electric field and are separated from the airflow, which are then ejected from the ion guide having the central axis different from the ion's entry axis, to be transported into the mass spectrometer. The charged droplets, which have high mass, are not separated from the airflow and, together with the airflow, are ejected from the outlet different from one for the ions. Electrically neutral droplets are insensitive to the electric field, and therefore those droplets, together with the airflow, are also ejected from the outlet different from one for ions.
Patent Literature 2 describes an ion guide having an ion outlet placed out of the ion's entry axis for separation between the charged droplets and the ions. The high-mass droplets travel together with the airflow in straight lines, and only the low-mass ions are transported to the outlet of the ion guide by an electric field, and then transported into the mass spectrometer.